Targeting heat shock proteins 70/90 and proteasome for cancer therapy

Current Medicinal Chemistry

Volumn 18, Issue 27, 2011, Pages 4250-4264

  Wang, R E ^a  

^a WASHINGTON UNIVERSITY   (United States)

Author keywords

26S proteasome; Cancer; Clinical trials; Heat shock protein 70 (HSP70); Heat shock protein 90 (HSP90); Proteasomal degradation; Simultaneous inhibition

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; ALVESPIMYCIN; ANTINEOPLASTIC AGENT; AT 13387; BEP 800; BIIB 021; BORTEZOMIB; CELASTROL; CUDC 305; EC 144; GAMBOGIC ACID; GELDANAMYCIN; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; KNK 437; KU 135; KW 2478; MG 115; NOVOBIOCIN; POCHONIN D; POCHOXIME A; POCHOXIME B; POCHOXIME C; PUH 71; RETASPIMYCIN; SNX 5422; TANESPIMYCIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VER 155008; WITHAFERIN A;

ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; CANCER INHIBITION; CANCER THERAPY; CYTOTOXICITY; DRUG BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; HUMAN; HYDROGEN BOND; LUNG NON SMALL CELL CANCER; LYMPHOMA; MYELOMA; NONHUMAN; PROTEIN EXPRESSION; REVIEW; UNSPECIFIED SIDE EFFECT;

ANIMALS; CELL LINE, TUMOR; HSP70 HEAT-SHOCK PROTEINS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROTEASOME ENDOPEPTIDASE COMPLEX; UBIQUITIN;

EID: 80052188068     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986711797189574     Document Type: Review

References (142)

1. Feige, U. Stress-inducible cellular responses. Birkhäuser Verlag: Basel, Boston, 1996.
2. Cokkinos, D.V. Myocardial ischemia from mechanisms to therapeutic potentials. Springer: New York, 2006.
3. Richter-Landsberg, C. Heat shock proteins in neural cells. Landes Bioscience; Springer Science+Business Media: Austin, Tex. New York, 2007.
4. Qian, S.B.; McDonough, H.; Boellmann, F.; Cyr, D.M.; Patterson, C. CHIPmediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature, 2006, 440, 551-555.
5. Mimnaugh, E.G.; Xu, W.; Vos, M.; Yuan, X.; Isaacs, J.S.; Bisht, K.S.; Gius, D.; Neckers, L. Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol. Cancer Ther., 2004, 3, 551-566. (Pubitemid 39193734)
6. Almond, J.B.; Cohen, G.M. The proteasome: a novel target for cancer chemotherapy. Leukemia, 2002, 16, 433-443. (Pubitemid 34449723)
7. Calderwood, S.K.; Ciocca, D.R. Heat shock proteins: stress proteins with Janus-like properties in cancer. Int. J. Hyperthermia, 2008, 24, 31-39. (Pubitemid 351167617)
8. Calderwood, S.K.; Khaleque, M.A.; Sawyer, D.B.; Ciocca, D.R. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem. Sci., 2006, 31, 164-172. (Pubitemid 43361923)
9. Mani, A.; Gelmann, E.P. The ubiquitin-proteasome pathway and its role in cancer. J. Clin. Oncol., 2005, 23, 4776-4789. (Pubitemid 46224082)
10. Pajonk, F.; McBride, W.H. The proteasome in cancer biology and treatment. Radiat. Res., 2001, 156, 447-459. (Pubitemid 33027513)
11. Rohde, M.; Daugaard, M.; Jensen, M.H.; Helin, K.; Nylandsted, J.; Jaattela, M. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes Dev., 2005, 19, 570-582. (Pubitemid 40314989)
12. Voorhees, P.M.; Dees, E.C.; O'Neil, B.; Orlowski, R.Z. The proteasome as a target for cancer therapy. Clin. Cancer Res., 2003, 9, 6316-6325. (Pubitemid 38031815)
13. Schlesinger, M.J. Heat shock proteins. J. Biol. Chem., 1990, 265, 12111-12114.
14. Morimoto, R.I. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev., 1998, 12, 3788-3796. (Pubitemid 29024840)
15. Shamovsky, I.; Nudler, E. New insights into the mechanism of heat shock response activation. Cell. Mol. Life. Sci., 2008, 65, 855-861.
16. Voellmy, R. On mechanisms that control heat shock transcription factor activity in metazoan cells. Cell Stress Chaperones, 2004, 9, 122-133. (Pubitemid 39013809)
17. Hartl, F.U. Molecular chaperones in cellular protein folding. Nature, 1996, 381, 571-579.
18. Mayer, M.P.; Bukau, B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell. Mol. Life Sci., 2005, 62, 670-684.
19. Song, Y.; Masison, D.C. Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1). J. Biol. Chem., 2005, 280, 34178-34185. (Pubitemid 41443142)
20. Nanbu, K.; Konishi, I.; Komatsu, T.; Mandai, M.; Yamamoto, S.; Kuroda, H.; Koshiyama, M.; Mori, T. Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression. Cancer, 1996, 77, 330-338. (Pubitemid 26023352)
21. Kaur, J.; Kaur, J.; Ralhan, R. Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells. Int. J. Cancer, 2000, 85, 1-5.
22. Maehara, Y.; Oki, E.; Abe, T.; Tokunaga, E.; Shibahara, K.; Kakeji, Y.; Sugimachi, K. Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer. Oncology, 2000, 58, 144-151. (Pubitemid 30113865)
23. Lazaris, A.C.; Theodoropoulos, G.E.; Davaris, P.S.; Panoussopoulos, D.; Nakopoulou, L.; Kittas, C.; Golematis, B.C. Heat shock protein 70 and HLADR molecules tissue expression. Prognostic implications in colorectal cancer. Dis. Colon Rectum, 1995, 38, 739-745.
24. Marunouchi, T.; Hosoya, H. Regulation of hsc70 expression in the human histiocytic lymphoma cell line, U937. Cell Struct. Funct., 1993, 18, 437-447. (Pubitemid 24119297)
25. Ciocca, D.R.; Clark, G.M.; Tandon, A.K.; Fuqua, S.A.; Welch, W.J.; McGuire, W.L. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J. Natl. Cancer Inst., 1993, 85, 570-574. (Pubitemid 23110932)
26. Ciocca, D.R.; Fuqua, S.A.; Lock-Lim, S.; Toft, D.O.; Welch, W.J.; McGuire, W.L. Response of human breast cancer cells to heat shock and chemotherapeutic drugs. Cancer Res., 1992, 52, 3648-3654.
27. Didelot, C.; Lanneau, D.; Brunet, M.; Joly, A.L.; De Thonel, A.; Chiosis, G.; Garrido, C. Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr. Med. Chem., 2007, 14, 2839-2847. (Pubitemid 350201651)
28. Hoffmann, T.; Hovemann, B. Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes encode formerly identified tumour-specific transplantation antigens. Gene, 1988, 74, 491-501. (Pubitemid 19060663)
29. Krone, P.H.; Sass, J.B. HSP 90 alpha and HSP 90 beta genes are present in the zebrafish and are differentially regulated in developing embryos. Biochem. Biophys. Res. Commun., 1994, 204, 746-752.
30. Rebbe, N.F.; Ware, J.; Bertina, R.M.; Modrich, P.; Stafford, D.W. Nucleotide sequence of a cDNA for a member of the human 90-kDa heat-shock protein family. Gene, 1987, 53, 235-245. (Pubitemid 17116365)
31. Csermely, P.; Schnaider, T.; Soti, C.; Prohaszka, Z.; Nardai, G. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol. Ther., 1998, 79, 129-168. (Pubitemid 28380440)
32. Massey, A.J. ATPases as drug targets: insights from heat shock proteins 70 and 90. J. Med. Chem., 2010, 53, 7280-7286.
33. Drysdale, M.J.; Brough, P.A.; Massey, A.; Jensen, M.R.; Schoepfer, J. Targeting Hsp90 for the treatment of cancer. Curr. Opin. Drug Discov. Devel., 2006, 9, 483-495. (Pubitemid 44081157)
34. Porter, J.R.; Fritz, C.C.; Depew, K.M. Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapy. Curr. Opin. Chem. Biol., 2010, 14, 412-420.
35. An, W.G.; Schulte, T.W.; Neckers, L.M. The heat shock protein 90 antagonist geldanamycin alters chaperone association with p210bcr-abl and v-src proteins before their degradation by the proteasome. Cell Growth Differ., 2000, 11, 355-360. (Pubitemid 30619563)
36. Stebbins, C.E.; Russo, A.A.; Schneider, C.; Rosen, N.; Hartl, F.U.; Pavletich, N.P. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell, 1997, 89, 239-250. (Pubitemid 27199896)
37. Prodromou, C.; Roe, S.M.; O'Brien, R.; Ladbury, J.E.; Piper, P.W.; Pearl, L.H. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell, 1997, 90, 65-75. (Pubitemid 28009419)
38. Schulte, T.W.; Neckers, L.M. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol., 1998, 42, 273-279. (Pubitemid 28393843)
39. Barluenga, S.; Fontaine, J.G.; Wang, C.; Aouadi, K.; Chen, R.; Beebe, K.; Neckers, L.; Winssinger, N. Inhibition of HSP90 with pochoximes: SAR and structure-based insights. Chembiochem, 2009, 10, 2753-2759.
40. Barluenga, S.; Wang, C.; Fontaine, J.G.; Aouadi, K.; Beebe, K.; Tsutsumi, S.; Neckers, L.; Winssinger, N. Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor. Angew. Chem. Int. Ed. Engl., 2008, 47, 4432-4435.
41. Tian, Z.Q.; Liu, Y.; Zhang, D.; Wang, Z.; Dong, S.D.; Carreras, C.W.; Zhou, Y.; Rastelli, G.; Santi, D.V.; Myles, D.C. Synthesis and biological activities of novel 17-aminogeldanamycin derivatives. Bioorg. Med. Chem., 2004, 12, 5317-5329. (Pubitemid 39243952)
42. Kang, B.H.; Plescia, J.; Song, H.Y.; Meli, M.; Colombo, G.; Beebe, K.; Scroggins, B.; Neckers, L.; Altieri, D.C. Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90. J. Clin. Invest., 2009, 119, 454-464.
43. Kang, B.H.; Siegelin, M.D.; Plescia, J.; Raskett, C.M.; Garlick, D.S.; Dohi, T.; Lian, J.B.; Stein, G.S.; Languino, L.R.; Altieri, D.C. Preclinical characterization of mitochondria-targeted small molecule hsp90 inhibitors, gamitrinibs, in advanced prostate cancer. Clin. Cancer Res., 2010, 16, 4779-4788.
44. Douglas, M.; Lim, A.R.; Porter, J.R.; West, K.; Pink, M.M.; Ge, J.; Wylie, A.A.; Tibbits, T.T.; Biggs, K.; Curtis, M.; Palombella, V.J.; Adams, J.; Fritz, C.C.; Normant, E. The antiproliferative activity of the heat shock protein 90 inhibitor IPI-504 is not dependent on NAD(P)H:quinone oxidoreductase 1 activity in vivo. Mol. Cancer Ther., 2009, 8, 3369-3378.
45. Leow, C.C.; Chesebrough, J.; Coffman, K.T.; Fazenbaker, C.A.; Gooya, J.; Weng, D.; Coats, S.; Jackson, D.; Jallal, B.; Chang, Y. Antitumor efficacy of IPI-504, a selective heat shock protein 90 inhibitor against human epidermal growth factor receptor 2-positive human xenograft models as a single agent and in combination with trastuzumab or lapatinib. Mol. Cancer Ther., 2009, 8, 2131-2141.
46. Tillotson, B.; Slocum, K.; Coco, J.; Whitebread, N.; Thomas, B.; West, K.A.; MacDougall, J.; Ge, J.; Ali, J.A.; Palombella, V.J.; Normant, E.; Adams, J.; Fritz, C.C. Hsp90 (heat shock protein 90) inhibitor occupancy is a direct determinant of client protein degradation and tumor growth arrest in vivo. J. Biol. Chem., 2010, 285, 39835-39843.
47. Sequist, L.V.; Gettinger, S.; Senzer, N.N.; Martins, R.G.; Janne, P.A.; Lilenbaum, R.; Gray, J.E.; Iafrate, A.J.; Katayama, R.; Hafeez, N.; Sweeney, J.; Walker, J.R.; Fritz, C.; Ross, R.W.; Grayzel, D.; Engelman, J.A.; Borger, D.R.; Paez, G.; Natale, R. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J. Clin. Oncol., 2010, 28, 4953-4960.
48. Kasibhatla, S.R.; Hong, K.; Biamonte, M.A.; Busch, D.J.; Karjian, P.L.; Sensintaffar, J.L.; Kamal, A.; Lough, R.E.; Brekken, J.; Lundgren, K.; Grecko, R.; Timony, G.A.; Ran, Y.; Mansfield, R.; Fritz, L.C.; Ulm, E.; Burrows, F.J.; Boehm, M.F. Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity. J. Med. Chem., 2007, 50, 2767-2778. (Pubitemid 46980848)
49. Workman, P. Auditing the pharmacological accounts for Hsp90 molecular chaperone inhibitors: unfolding the relationship between pharmacokinetics and pharmacodynamics. Mol. Cancer Ther., 2003, 2, 131-138.
50. Yun, T.J.; Harning, E.K.; Giza, K.; Rabah, D.; Li, P.; Arndt, J.W.; Luchetti, D.; Biamonte, M.A.; Shi, J.; Lundgren, K.; Manning, A.; Kehry, M.R. EC144, a synthetic inhibitor of heat shock protein 90, blocks innate and adaptive immune responses in models of inflammation and autoimmunity. J. Immunol., 2010, 186, 563-575.
51. Usmani, S.Z.; Bona, R.D.; Chiosis, G.; Li, Z. The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. J. Hematol. Oncol., 2010, 3, 40.
52. Caldas-Lopes, E.; Cerchietti, L.; Ahn, J.H.; Clement, C.C.; Robles, A.I.; Rodina, A.; Moulick, K.; Taldone, T.; Gozman, A.; Guo, Y.; Wu, N.; de Stanchina, E.; White, J.; Gross, S.S.; Ma, Y.; Varticovski, L.; Melnick, A.; Chiosis, G. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl. Acad. Sci. U S A, 2009, 106, 8368-8373.
53. Bao, R.; Lai, C.J.; Wang, D.G.; Qu, H.; Yin, L.; Zifcak, B.; Tao, X.; Wang, J.; Atoyan, R.; Samson, M.; Forrester, J.; Xu, G.X.; DellaRocca, S.; Borek, M.; Zhai, H.X.; Cai, X.; Qian, C. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol. Cancer Ther., 2009, 8, 3296-3306.
54. Bao, R.; Lai, C.J.; Qu, H.; Wang, D.; Yin, L.; Zifcak, B.; Atoyan, R.; Wang, J.; Samson, M.; Forrester, J.; DellaRocca, S.; Xu, G.X.; Tao, X.; Zhai, H.X.; Cai, X.; Qian, C. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin. Cancer Res., 2009, 15, 4046-4057.
55. Brough, P.A.; Barril, X.; Borgognoni, J.; Chene, P.; Davies, N.G.; Davis, B.; Drysdale, M.J.; Dymock, B.; Eccles, S.A.; Garcia-Echeverria, C.; Fromont, C.; Hayes, A.; Hubbard, R.E.; Jordan, A.M.; Jensen, M.R.; Massey, A.; Merrett, A.; Padfield, A.; Parsons, R.; Radimerski, T.; Raynaud, F.I.; Robertson, A.; Roughley, S.D.; Schoepfer, J.; Simmonite, H.; Sharp, S.Y.; Surgenor, A.; Valenti, M.; Walls, S.; Webb, P.; Wood, M.; Workman, P.; Wright, L. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J. Med. Chem., 2009, 52, 4794-4809.
56. Massey, A.J.; Schoepfer, J.; Brough, P.A.; Brueggen, J.; Chene, P.; Drysdale, M.J.; Pfaar, U.; Radimerski, T.; Ruetz, S.; Schweitzer, A.; Wood, M.; Garcia- Echeverria, C.; Jensen, M.R. Preclinical antitumor activity of the orally available heat shock protein 90 inhibitor NVP-BEP800. Mol. Cancer Ther., 2010, 9, 906-919.
57. Stuhmer, T.; Chatterjee, M.; Grella, E.; Seggewiss, R.; Langer, C.; Muller, S.; Schoepfer, J.; Garcia-Echeverria, C.; Quadt, C.; Jensen, M.R.; Einsele, H.; Bargou, R.C. Anti-myeloma activity of the novel 2- aminothienopyrimidine Hsp90 inhibitor NVP-BEP800. Br. J. Haematol., 2009, 147, 319-327.
58. Besant, P.G.; Lasker, M.V.; Bui, C.D.; Turck, C.W. Inhibition of branchedchain alpha-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol. Mol. Pharmacol., 2002, 62, 289-296. (Pubitemid 34804108)
59. Wang, C.; Barluenga, S.; Koripelly, G.K.; Fontaine, J.G.; Chen, R.; Yu, J.C.; Shen, X.; Chabala, J.C.; Heck, J.V.; Rubenstein, A.; Winssinger, N. Synthesis of pochoxime prodrugs as potent HSP90 inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 3836-3840.
60. Zhu, H.; Woolfenden, S.; Bronson, R.T.; Jaffer, Z.M.; Barluenga, S.; Winssinger, N.; Rubenstein, A.E.; Chen, R.; Charest, A. The novel Hsp90 inhibitor NXD30001 induces tumor regression in a genetically engineered mouse model of glioblastoma multiforme. Mol. Cancer Ther., 2010, 9, 2618-2626.
61. Eccles, S.A.; Massey, A.; Raynaud, F.I.; Sharp, S.Y.; Box, G.; Valenti, M.; Patterson, L.; de Haven Brandon, A.; Gowan, S.; Boxall, F.; Aherne, W.; Rowlands, M.; Hayes, A.; Martins, V.; Urban, F.; Boxall, K.; Prodromou, C.; Pearl, L.; James, K.; Matthews, T.P.; Cheung, K.M.; Kalusa, A.; Jones, K.; McDonald, E.; Barril, X.; Brough, P.A.; Cansfield, J.E.; Dymock, B.; Drysdale, M.J.; Finch, H.; Howes, R.; Hubbard, R.E.; Surgenor, A.; Webb, P.; Wood, M.; Wright, L.; Workman, P. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res., 2008, 68, 2850-2860. (Pubitemid 351556284)
62. Gaspar, N.; Sharp, S.Y.; Eccles, S.A.; Gowan, S.; Popov, S.; Jones, C.; Pearson, A.; Vassal, G.; Workman, P. Mechanistic evaluation of the novel HSP90 inhibitor NVP-AUY922 in adult and pediatric glioblastoma. Mol. Cancer Ther., 2010, 9, 1219-1233.
63. Nakashima, T.; Ishii, T.; Tagaya, H.; Seike, T.; Nakagawa, H.; Kanda, Y.; Akinaga, S.; Soga, S.; Shiotsu, Y. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin. Cancer Res., 2010, 16, 2792-2802.
64. Woodhead, A.J.; Angove, H.; Carr, M.G.; Chessari, G.; Congreve, M.; Coyle, J.E.; Cosme, J.; Graham, B.; Day, P.J.; Downham, R.; Fazal, L.; Feltell, R.; Figueroa, E.; Frederickson, M.; Lewis, J.; McMenamin, R.; Murray, C.W.; O'Brien, M.A.; Parra, L.; Patel, S.; Phillips, T.; Rees, D.C.; Rich, S.; Smith, D.M.; Trewartha, G.; Vinkovic, M.; Williams, B.; Woolford, A.J. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-di hydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J. Med. Chem., 2010, 53, 5956-5969.
65. Brough, P.A.; Aherne, W.; Barril, X.; Borgognoni, J.; Boxall, K.; Cansfield, J.E.; Cheung, K.M.; Collins, I.; Davies, N.G.; Drysdale, M.J.; Dymock, B.; Eccles, S.A.; Finch, H.; Fink, A.; Hayes, A.; Howes, R.; Hubbard, R.E.; James, K.; Jordan, A.M.; Lockie, A.; Martins, V.; Massey, A.; Matthews, T.P.; McDonald, E.; Northfield, C.J.; Pearl, L.H.; Prodromou, C.; Ray, S.; Raynaud, F.I.; Roughley, S.D.; Sharp, S.Y.; Surgenor, A.; Walmsley, D.L.; Webb, P.; Wood, M.; Workman, P.; Wright, L. 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J. Med. Chem., 2008, 51, 196-218.
66. Fadden, P.; Huang, K.H.; Veal, J.M.; Steed, P.M.; Barabasz, A.F.; Foley, B.; Hu, M.; Partridge, J.M.; Rice, J.; Scott, A.; Dubois, L.G.; Freed, T.A.; Silinski, M.A.; Barta, T.E.; Hughes, P.F.; Ommen, A.; Ma, W.; Smith, E.D.; Spangenberg, A.W.; Eaves, J.; Hanson, G.J.; Hinkley, L.; Jenks, M.; Lewis, M.; Otto, J.; Pronk, G.J.; Verleysen, K.; Haystead, T.A.; Hall, S.E. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90. Chem. Biol., 2010, 17, 686-694.
67. Huang, K.H.; Veal, J.M.; Fadden, R.P.; Rice, J.W.; Eaves, J.; Strachan, J.P.; Barabasz, A.F.; Foley, B.E.; Barta, T.E.; Ma, W.; Silinski, M.A.; Hu, M.; Partridge, J.M.; Scott, A.; DuBois, L.G.; Freed, T.; Steed, P.M.; Ommen, A.J.; Smith, E.D.; Hughes, P.F.; Woodward, A.R.; Hanson, G.J.; McCall, W.S.; Markworth, C.J.; Hinkley, L.; Jenks, M.; Geng, L.; Lewis, M.; Otto, J.; Pronk, B.; Verleysen, K.; Hall, S.E. Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J. Med. Chem., 2009, 52, 4288-4305.
68. Zhai, Q.Q.; Gong, G.Q.; Liu, Z.; Luo, Y.; Xia, M.; Xing, G.W.; You, X.F.; Wang, Y.F. Preclinical pharmacokinetic analysis of SNX-2112, a novel Hsp90 inhibitor, in rats. Biomed. Pharmacother., 2011, 65, 132-136
69. Best, O.G.; Singh, N.; Forsyth, C.; Mulligan, S.P. The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway. Br. J. Haematol., 2010, 151, 185-188.
70. Dutta, R.; Inouye, M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci., 2000, 25, 24-28.
71. Roughley, S.; Wright, L.; Brough, P.; Massey, A.; Hubbard, R.E. Hsp90 Inhibitors and Drugs from Fragment and Virtual Screening. Top. Curr. Chem., 2011
72. Davenport, J.; Manjarrez, J.R.; Peterson, L.; Krumm, B.; Blagg, B.S.; Matts, R.L. Gambogic Acid, a natural product inhibitor of hsp90. J. Nat. Prod., 2011, 74, 1085-1092.
73. Li, Y.; Zhang, T.; Jiang, Y.; Lee, H.F.; Schwartz, S.J.; Sun, D. (-)- Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line Mia Paca-2. Mol. Pharm., 2009, 6, 1152-1159.
74. Yin, Z.; Henry, E.C.; Gasiewicz, T.A. (-)-Epigallocatechin-3-gallate is a novel Hsp90 inhibitor. Biochemistry, 2009, 48, 336-345.
75. Tran, P.L.; Kim, S.A.; Choi, H.S.; Yoon, J.H.; Ahn, S.G. Epigallocatechin-3- gallate suppresses the expression of HSP70 and HSP90 and exhibits antitumor activity in vitro and in vivo. BMC Cancer, 2010, 10, 276.
76. Marcu, M.G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers, L.M. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem., 2000, 275, 37181-37186. (Pubitemid 32002137)
77. Marcu, M.G.; Schulte, T.W.; Neckers, L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J. Natl. Cancer Inst., 2000, 92, 242-248. (Pubitemid 30099783)
78. Burlison, J.A.; Avila, C.; Vielhauer, G.; Lubbers, D.J.; Holzbeierlein, J.; Blagg, B.S. Development of novobiocin analogues that manifest antiproliferative activity against several cancer cell lines. J. Org. Chem., 2008, 73, 2130-2137. (Pubitemid 351497740)
79. Shelton, S.N.; Shawgo, M.E.; Matthews, S.B.; Lu, Y.; Donnelly, A.C.; Szabla, K.; Tanol, M.; Vielhauer, G.A.; Rajewski, R.A.; Matts, R.L.; Blagg, B.S.; Robertson, J.D. KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells. Mol. Pharmacol., 2009, 76, 1314-1322.
80. Audisio, D.; Messaoudi, S.; Cegielkowski, L.; Peyrat, J.F.; Brion, J.D.; Methy-Gonnot, D.; Radanyi, C.; Renoir, J.M.; Alami, M. Discovery and biological activity of 6BrCaQ as an inhibitor of the Hsp90 protein folding machinery. ChemMedChem, 2011, 6, 804-815.
81. Lu, Z.; Jin, Y.; Qiu, L.; Lai, Y.; Pan, J. Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation. Cancer Lett., 2010, 290, 182-191.
82. Yu, Y.; Hamza, A.; Zhang, T.; Gu, M.; Zou, P.; Newman, B.; Li, Y.; Gunatilaka, A.A.; Zhan, C.G.; Sun, D. Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem. Pharmacol., 2010, 79, 542-551.
83. Zhang, T.; Li, Y.; Yu, Y.; Zou, P.; Jiang, Y.; Sun, D. Characterization of celastrol to inhibit hsp90 and cdc37 interaction. J. Biol. Chem., 2009, 284, 35381-35389.
84. Peng, B.; Xu, L.; Cao, F.; Wei, T.; Yang, C.; Uzan, G.; Zhang, D. HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way. Mol. Cancer, 2010, 9, 79.
85. Ghoshal, S.; Rao, I.; Earp, J.C.; Jusko, W.J.; Wetzler, M. Down-regulation of heat shock protein 70 improves arsenic trioxide and 17-DMAG effects on constitutive signal transducer and activator of transcription 3 activity. Cancer Chemother. Pharmacol., 2010, 66, 681-689.
86. Guo, F.; Rocha, K.; Bali, P.; Pranpat, M.; Fiskus, W.; Boyapalle, S.; Kumaraswamy, S.; Balasis, M.; Greedy, B.; Armitage, E.S.; Lawrence, N.; Bhalla, K. Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylaminodemethoxy geldanamycin. Cancer Res., 2005, 65, 10536-10544. (Pubitemid 41743748)
87. Phillips, P.A.; Dudeja, V.; McCarroll, J.A.; Borja-Cacho, D.; Dawra, R.K.; Grizzle, W.E.; Vickers, S.M.; Saluja, A.K. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res., 2007, 67, 9407-9416. (Pubitemid 47535931)
88. Westerheide, S.D.; Kawahara, T.L.; Orton, K.; Morimoto, R.I. Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J. Biol. Chem., 2006, 281, 9616-9622. (Pubitemid 43864680)
89. Vispe, S.; DeVries, L.; Creancier, L.; Besse, J.; Breand, S.; Hobson, D.J.; Svejstrup, J.Q.; Annereau, J.P.; Cussac, D.; Dumontet, C.; Guilbaud, N.; Barret, J.M.; Bailly, C. Triptolide is an inhibitor of RNA polymerase I and II-dependent transcription leading predominantly to down-regulation of short-lived mRNA. Mol. Cancer Ther., 2009, 8, 2780-2790.
90. Hikim, A.P.; Lue, Y.H.; Wang, C.; Reutrakul, V.; Sangsuwan, R.; Swerdloff, R.S. Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure. J. Androl., 2000, 21, 431-437. (Pubitemid 30252515)
91. Liu, L.; Jiang, Z.; Liu, J.; Huang, X.; Wang, T.; Liu, J.; Zhang, Y.; Zhou, Z.; Guo, J.; Yang, L.; Chen, Y.; Zhang, L. Sex differences in subacute toxicity and hepatic microsomal metabolism of triptolide in rats. Toxicology, 2010, 271, 57-63.
92. Xu, L.; Chen, H.; Xu, H.; Yang, X. Anti-tumour and immuno-modulation effects of triptolide-loaded polymeric micelles. Eur. J. Pharm. Biopharm., 2008, 70, 741-748.
93. Yao, J.; Jiang, Z.; Duan, W.; Huang, J.; Zhang, L.; Hu, L.; He, L.; Li, F.; Xiao, Y.; Shu, B.; Liu, C. Involvement of mitochondrial pathway in triptolide- induced cytotoxicity in human normal liver L-02 cells. Biol. Pharm. Bull., 2008, 31, 592-597. (Pubitemid 351500486)
94. Wang, R.E.; Kao, J.L.; Hilliard, C.A.; Pandita, R.K.; Roti Roti, J.L.; Hunt, C.R.; Taylor, J.S. Inhibition of heat shock induction of heat shock protein 70 and enhancement of heat shock protein 27 phosphorylation by quercetin derivatives. J. Med. Chem., 2009, 52, 1912-1921.
95. Formica, J.V.; Regelson, W. Review of the biology of Quercetin and related bioflavonoids. Food Chem. Toxicol., 1995, 33, 1061-1080. (Pubitemid 26009773)
96. Brierley-Hobson, S. Binding of (-)-epigallocatechin-3-gallate to the Hsp70 ATPase domain may promote apoptosis in colorectal cancer. Bioscience Horizons, 2008, 1, 9-18.
97. Koishi, M.; Yokota, S.; Mae, T.; Nishimura, Y.; Kanamori, S.; Horii, N.; Shibuya, K.; Sasai, K.; Hiraoka, M. The effects of KNK437, a novel inhibitor of heat shock protein synthesis, on the acquisition of thermotolerance in a murine transplantable tumor in vivo. Clin. Cancer Res., 2001, 7, 215-219. (Pubitemid 32110226)
98. Yokota, S.; Kitahara, M.; Nagata, K. Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells. Cancer Res., 2000, 60, 2942-2948. (Pubitemid 30395819)
99. Williamson, D.S.; Borgognoni, J.; Clay, A.; Daniels, Z.; Dokurno, P.; Drysdale, M.J.; Foloppe, N.; Francis, G.L.; Graham, C.J.; Howes, R.; Macias, A.T.; Murray, J.B.; Parsons, R.; Shaw, T.; Surgenor, A.E.; Terry, L.; Wang, Y.; Wood, M.; Massey, A.J. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J. Med. Chem., 2009, 52, 1510-1513.
100. Massey, A.J.; Williamson, D.S.; Browne, H.; Murray, J.B.; Dokurno, P.; Shaw, T.; Macias, A.T.; Daniels, Z.; Geoffroy, S.; Dopson, M.; Lavan, P.; Matassova, N.; Francis, G.L.; Graham, C.J.; Parsons, R.; Wang, Y.; Padfield, A.; Comer, M.; Drysdale, M.J.; Wood, M. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother. Pharmacol., 2010, 66, 535-545.
101. Flaherty, K.M.; DeLuca-Flaherty, C.; McKay, D.B. Three-dimensional structure of the ATPase fragment of a 70K heat-shock cognate protein. Nature, 1990, 346, 623-628.
102. Evans, C.G.; Chang, L.; Gestwicki, J.E. Heat Shock Protein 70 (Hsp70) as an Emerging Drug Target. J. Med. Chem., 2010, 53, 4585-4602.
103. Jinwal, U.K.; Miyata, Y.; Koren, J., 3rd; Jones, J.R.; Trotter, J.H.; Chang, L.; O'Leary, J.; Morgan, D.; Lee, D.C.; Shults, C.L.; Rousaki, A.; Weeber, E.J.; Zuiderweg, E.R.; Gestwicki, J.E.; Dickey, C.A. Chemical manipulation of hsp70 ATPase activity regulates tau stability. J. Neurosci., 2009, 29, 12079-12088.
104. Wang, A.M.; Morishima, Y.; Clapp, K.M.; Peng, H.M.; Pratt, W.B.; Gestwicki, J.E.; Osawa, Y.; Lieberman, A.P. Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation. J. Biol. Chem., 2010, 285, 15714-15723.
105. Leu, J.I.; Pimkina, J.; Frank, A.; Murphy, M.E.; George, D.L. A small molecule inhibitor of inducible heat shock protein 70. Mol. Cell., 2009, 36, 15-27.
106. Rerole, A.L.; Gobbo, J.; De Thonel, A.; Schmitt, E.; Pais de Barros, J.P.; Hammann, A.; Lanneau, D.; Fourmaux, E.; Deminov, O.; Micheau, O.; Lagrost, L.; Colas, P.; Kroemer, G.; Garrido, C. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res., 2011, 71, 484-495.
107. Davenport, E.L.; Zeisig, A.; Aronson, L.I.; Moore, H.E.; Hockley, S.; Gonzalez, D.; Smith, E.M.; Powers, M.V.; Sharp, S.Y.; Workman, P.; Morgan, G.J.; Davies, F.E. Targeting heat shock protein 72 enhances Hsp90 inhibitorinduced apoptosis in myeloma. Leukemia, 2010, 24, 1804-1807.
108. Voges, D.; Zwickl, P.; Baumeister, W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu. Rev. Biochem., 1999, 68, 1015-1068. (Pubitemid 29449214)
109. Wang, J.; Maldonado, M.A. The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell. Mol. Immunol., 2006, 3, 255-261.
110. Nandi, D.; Tahiliani, P.; Kumar, A.; Chandu, D. The ubiquitin-proteasome system. J. Biosci., 2006, 31, 137-155.
111. Nawrocki, S.T.; Sweeney-Gotsch, B.; Takamori, R.; McConkey, D.J. The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol. Cancer Ther., 2004, 3, 59-70. (Pubitemid 39193679)
112. O'Connor, O.A.; Wright, J.; Moskowitz, C.; Muzzy, J.; MacGregor-Cortelli, B.; Stubblefield, M.; Straus, D.; Portlock, C.; Hamlin, P.; Choi, E.; Dumetrescu, O.; Esseltine, D.; Trehu, E.; Adams, J.; Schenkein, D.; Zelenetz, A.D. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J. Clin. Oncol., 2005, 23, 676-684. (Pubitemid 46237441)
113. Shah, S.A.; Potter, M.W.; McDade, T.P.; Ricciardi, R.; Perugini, R.A.; Elliott, P.J.; Adams, J.; Callery, M.P. 26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer. J. Cell. Biochem., 2001, 82, 110-122.
114. Luo, J.; Solimini, N.L.; Elledge, S.J. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell, 2009, 136, 823-837.
115. Adams, J.; Palombella, V.J.; Sausville, E.A.; Johnson, J.; Destree, A.; Lazarus, D.D.; Maas, J.; Pien, C.S.; Prakash, S.; Elliott, P.J. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res., 1999, 59, 2615-2622. (Pubitemid 29269108)
116. Fisher, R.I.; Bernstein, S.H.; Kahl, B.S.; Djulbegovic, B.; Robertson, M.J.; de Vos, S.; Epner, E.; Krishnan, A.; Leonard, J.P.; Lonial, S.; Stadtmauer, E.A.; O'Connor, O.A.; Shi, H.; Boral, A.L.; Goy, A. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma.J. Clin. Oncol., 2006, 24, 4867-4874. (Pubitemid 46655613)
117. Bush, K.T.; Goldberg, A.L.; Nigam, S.K. Proteasome inhibition leads to a heat-shock response, induction of endoplasmic reticulum chaperones, and thermotolerance. J. Biol. Chem., 1997, 272, 9086-9092. (Pubitemid 27154911)
118. Rock, K.L.; Gramm, C.; Rothstein, L.; Clark, K.; Stein, R.; Dick, L.; Hwang, D.; Goldberg, A.L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell, 1994, 78, 761-771. (Pubitemid 24294452)
119. Bogyo, M.; McMaster, J.S.; Gaczynska, M.; Tortorella, D.; Goldberg, A.L.; Ploegh, H. Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc. Natl. Acad. Sci. U S A, 1997, 94, 6629-6634.
120. Fenteany, G.; Standaert, R.F.; Lane, W.S.; Choi, S.; Corey, E.J.; Schreiber, S.L. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science, 1995, 268, 726-731.
121. Laurent, N.; de Bouard, S.; Guillamo, J.S.; Christov, C.; Zini, R.; Jouault, H.; Andre, P.; Lotteau, V.; Peschanski, M. Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Mol. Cancer Ther., 2004, 3, 129-136. (Pubitemid 39193687)
122. Schmidtke, G.; Holzhutter, H.G.; Bogyo, M.; Kairies, N.; Groll, M.; de Giuli, R.; Emch, S.; Groettrup, M. How an inhibitor of the HIV-I protease modulates proteasome activity. J. Biol. Chem., 1999, 274, 35734-35740. (Pubitemid 129512875)
123. Mimnaugh, E.G.; Chavany, C.; Neckers, L. Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. J. Biol. Chem., 1996, 271, 22796-22801. (Pubitemid 26304727)
124. Neckers, L.; Schulte, T.W.; Mimnaugh, E. Geldanamycin as a potential anticancer agent: its molecular target and biochemical activity. Invest. New Drugs, 1999, 17, 361-373. (Pubitemid 30135903)
125. Lecomte, S.; Desmots, F.; Le Masson, F.; Le Goff, P.; Michel, D.; Christians, E.S.; Le Drean, Y. Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability. Oncogene, 2010, 29, 4216-4224.
126. Mathew, A.; Mathur, S.K.; Morimoto, R.I. Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway. Mol. Cell. Biol., 1998, 18, 5091-5098. (Pubitemid 28388092)
127. Stangl, K.; Gunther, C.; Frank, T.; Lorenz, M.; Meiners, S.; Ropke, T.; Stelter, L.; Moobed, M.; Baumann, G.; Kloetzel, P.M.; Stangl, V. Inhibition of the ubiquitin-proteasome pathway induces differential heat-shock protein response in cardiomyocytes and renders early cardiac protection. Biochem. Biophys. Res. Commun., 2002, 291, 542-549. (Pubitemid 34687378)
128. Lee, D.H.; Goldberg, A.L. Proteasome inhibitors cause induction of heat shock proteins and trehalose, which together confer thermotolerance in Saccharomyces cerevisiae. Mol. Cell. Biol., 1998, 18, 30-38. (Pubitemid 28021014)
129. Grossin, L.; Etienne, S.; Gaborit, N.; Pinzano, A.; Cournil-Henrionnet, C.; Gerard, C.; Payan, E.; Netter, P.; Terlain, B.; Gillet, P. Induction of heat shock protein 70 (Hsp70) by proteasome inhibitor MG 132 protects articular chondrocytes from cellular death in vitro and in vivo. Biorheology, 2004, 41, 521-534. (Pubitemid 39277108)
130. Robertson, J.D.; Datta, K.; Biswal, S.S.; Kehrer, J.P. Heat-shock protein 70 antisense oligomers enhance proteasome inhibitor-induced apoptosis. Biochem. J., 1999, 344 Pt 2, 477-485. (Pubitemid 30011605)
131. Yerlikaya, A.; Okur, E.; S, E.; Erin, N. Combined effects of the proteasome inhibitor bortezomib and Hsp70 inhibitors on the B16F10 melanoma cell line. Mol. Med. Report, 2010, 3, 333-339.
132. Roue, G.; Perez-Galan, P.; Mozos, A.; Lopez-Guerra, M.; Xargay-Torrent, S.; Rosich, L.; Saborit-Villarroya, I.; Normant, E.; Campo, E.; Colomer, D. The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78. Blood, 2011, 117, 1270-1279.
133. Awasthi, N.; Wagner, B.J. Heat Shock Protein Induction Is Required for Proteasome Inhibitor-Mediated Rescue From Apoptosis. Invest. Ophthalmol. Vis. Sci., 2005, 46, 3608-.
134. Sreedhar, A.S.; Soti, C.; Csermely, P. Inhibition of Hsp90: a new strategy for inhibiting protein kinases. Biochim. Biophys. Acta., 2004, 1697, 233-242. (Pubitemid 38326775)
135. Sreedhar, A.S.; Mihaly, K.; Pato, B.; Schnaider, T.; Stetak, A.; Kis-Petik, K.; Fidy, J.; Simonics, T.; Maraz, A.; Csermely, P. Hsp90 inhibition accelerates cell lysis. Anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide- and Hsp90-dependent events. J. Biol. Chem., 2003, 278, 35231-35240. (Pubitemid 37102289)
136. Boudeau, J.; Deak, M.; Lawlor, M.A.; Morrice, N.A.; Alessi, D.R. Heatshock protein 90 and Cdc37 interact with LKB1 and regulate its stability. Biochem. J., 2003, 370, 849-857. (Pubitemid 36399076)
137. Koga, F.; Xu, W.; Karpova, T.S.; McNally, J.G.; Baron, R.; Neckers, L. Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation. Proc. Natl. Acad. Sci. U S A, 2006, 103, 11318-11322. (Pubitemid 44156515)
138. Hunt, C.R.; Dix, D.J.; Sharma, G.G.; Pandita, R.K.; Gupta, A.; Funk, M.; Pandita, T.K. Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice. Mol. Cell. Biol., 2004, 24, 899-911. (Pubitemid 38057939)
139. Singleton, K.D.; Wischmeyer, P.E. Effects of HSP70.1/3 gene knockout on acute respiratory distress syndrome and the inflammatory response following sepsis. Am. J. Physiol. Lung Cell. Mol. Physiol., 2006, 290, L956-961. (Pubitemid 43725057)
140. Colson, K.; Doss, D.S.; Swift, R.; Tariman, J. Expanding role of bortezomib in multiple myeloma: nursing implications. Cancer Nurs., 2008, 31, 239-249. (Pubitemid 351652222)
141. Aalinkeel, R.; Bindukumar, B.; Reynolds, J.L.; Sykes, D.E.; Mahajan, S.D.; Chadha, K.C.; Schwartz, S.A. The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90. Prostate, 2008, 68, 1773-1789.
142. Chen, D.; Daniel, K.G.; Chen, M.S.; Kuhn, D.J.; Landis-Piwowar, K.R.; Dou, Q.P. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem. Pharmacol., 2005, 69, 1421-1432. (Pubitemid 40602442)